Predicting Inflammatory Arthritis in At-Risk Persons: Development of Scores for Risk Stratification

Duquenne, Laurence; Hensor, Elizabeth M A; Wilson, Michelle; Garcia-Montoya, Leticia; Nam, J.; Wu, Jianhua; Anioke, Innocent Chidi; Matteo, Andrea Di; Chowdhury, Rahaymin; Sidhu, Navkiran; Ponchel, Frédérique; Mankia, Kulveer; Emery, Paul

doi:10.7326/m23-0272

Cited by 17 publications

(2 citation statements)

References 49 publications

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“…The development of inflammatory arthritis was used as the outcome measure for the construction and validation of our model, rather than the full fulfilment of the 2010 RA ACR/EULAR classification criteria [ 37 ]. This methodological approach aligns with previous studies of our research group as well as with studies from other RA at-risk cohorts [ 7 , 10 , 38–40 ]. Moreover, we chose inflammatory arthritis development at the outcome measure as we felt that this is associated with management decisions in clinical practice, i.e.…”

Section: Discussionsupporting

confidence: 69%

Ultrasound in anti-CCP+ at-risk individuals without clinical synovitis: development of a novel 6-joint protocol for feasible risk prediction

Di Matteo,

De Lorenzis,

Duquenne

et al. 2023

Rheumatology

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Objectives To investigate, in anti-CCP antibody–positive individuals with musculoskeletal symptoms but no clinical synovitis (CCP+ at-risk), the additional value of US for the prediction of inflammatory arthritis. Furthermore, to define a concise US protocol for feasible risk prediction. Methods Demographic and clinical data were collected in 417 CCP+ at-risk (Leeds CCP cohort) with a baseline US scan assessing synovitis and bone erosions in 36 joints, and a follow-up duration ≥24 months. Multivariable binary regression models for inflammatory arthritis development at 24 months evaluated routine clinical variables associated with inflammatory arthritis alone (‘clinical’ model) and combined with a 36-joint US scanning protocol (‘clinical-US extended’ model). A ‘clinical-US short’ model was also developed. Results At 24 months, 92/417 (22.1%) CCP+ at-risk developed inflammatory arthritis (median time 7 months, interquartile range 3–12). The ‘clinical-US extended’ model performed better than the ‘clinical’ model [area under the curve (AUC) 0.788 vs AUC 0.731, respectively, P < 0.001] with an odds ratio for inflammatory arthritis development of 3.18 (95% CI 1.80–5.63) for US synovitis and 2.54 (95% CI 1.21–5.37) for bone erosions. The ‘clinical-US short’ model, which retained the wrists, knees and MTP5 joints, performed better (AUC 0.782) than the ‘clinical’ model (P < 0.001) and similarly (difference in Akaike information criteria <2) to the ‘clinical-US extended’ model. Conclusions US provides valuable information for predicting progression to inflammatory arthritis in CCP+ individuals both alone and in addition to clinical variables. US synovitis was associated with a 3-fold increase risk of inflammatory arthritis development. A concise US protocol of six joints provides clinically feasible risk prediction in CCP+ at-risk.

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Section: Discussionsupporting

confidence: 69%

Ultrasound in anti-CCP+ at-risk individuals without clinical synovitis: development of a novel 6-joint protocol for feasible risk prediction

Di Matteo,

De Lorenzis,

Duquenne

et al. 2023

Rheumatology

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“…Lancet Rheumatol 2024; e72-80. This study that used the same cohort as used by Duquenne et al [11] demonstrated that a subset of ACPA(þ) individuals had disappearance of subclinical synovitis as seen on ultrasound; this disappearance was associated with lower anti-CCP level, negative rheumatoid factor and fewer joints with ultrasound inflammation. This highlights that subclinical synovitis is not always associated with persistence or progression to clinical RA.…”

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confidence: 80%

Rheumatoid arthritis: prediction of future clinically-apparent disease, and prevention

Deane

2024

Current Opinion in Rheumatology

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Purpose of review This review discusses updates in the prediction and prevention of future rheumatoid arthritis (RA). Recent findings In individuals with musculoskeletal symptoms and elevated antibodies to citrullinated proteins (ACPA) without clinical inflammatory arthritis (IA), a ‘simple’ score has a positive predictive value (PPV) of ∼28% for clinical IA/RA within 1 year, and a comprehensive score (including ultrasound) has a PPV of ∼71% for clinical RA within 5 years. Controlled clinical trials in individuals at-risk for future RA have been performed using corticosteroids, rituximab, atorvastatin, methotrexate, hydroxychloroquine and abatacept. Abatacept modestly reduced rates of incident clinical RA and imaging inflammation within the trials, rituximab delayed clinical IA, and methotrexate improved function, symptoms and imaging inflammation. Vitamin D with or without omega 3 fatty acids reduced incidence of autoimmune diseases, including RA. While not proven in controlled clinical trials, observational studies suggest exercise, weight loss and smoking cessation may reduce progression to clinical RA. Summary Prediction and prevention of RA is advancing although there are no currently approved interventions for prevention. Future studies should include deeper evaluation of the pathophysiology of RA development to improve prediction and identify key pathways to target in future clinical trials, as well as develop infrastructure to support prevention-related research.

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Multi‐Autoantibody Testing Identifies Expansion of Reactivity to Targeted Antigens Before a Diagnosis of Rheumatoid Arthritis

Goff,

Bergstedt,

Feser

et al. 2024

ACR Open Rheumatology

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ObjectiveRheumatoid arthritis (RA) has a “pre‐RA” period in which multiple autoantibodies, including antibodies to citrullinated (cit) proteins (ACPA), rheumatoid factor (RF), anti–peptidyl arginine deiminase (anti‐PAD), among others, have been described; however, few studies have tested all autoantibodies in a single pre‐RA cohort. This study aims to evaluate the prevalence of multiple autoantibodies in pre‐RA and potentially identify an autoantibody profile in pre‐RA that indicates imminent onset of clinical RA.MethodsWe evaluated 148 individuals with two pre‐ and one post‐RA diagnosis samples available from the Department of Defense Serum Repository and matched controls. Samples were tested for immuglobulin (Ig) G anti–cyclic cit peptide‐3 (anti‐CCP3), five ACPA fine specificities, five anti‐PAD isoforms, as well as RF IgA and RF IgM using commercial platforms; cutoffs were determined using levels present in <1% of controls.ResultsPositivity of anti‐CCP3, RF IgA and RF IgM, anti‐PAD1, anti–cit‐vimentin 2, anti–cit‐fibrinogen, and anti–cit‐histone 1 increased over time in pre‐RA, although anti‐PAD and ACPA fine specificities were predominately present within anti‐CCP3–positive individuals. Within anti‐CCP3–positive samples from the pre‐RA period, positivity for RFs as well as anti‐PAD and ACPA fine specificities classified samples as being closer to the time of RA diagnosis.ConclusionMultiple autoantibodies are present in pre‐RA and increase in positivity as the time of RA diagnosis approaches. These results confirm previous findings predicting imminent RA and provide a pathway using commercial‐grade assays to assess the risk for and timing of development of clinical RA.

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Predicting Inflammatory Arthritis in At-Risk Persons: Development of Scores for Risk Stratification

Cited by 17 publications

References 49 publications

Ultrasound in anti-CCP+ at-risk individuals without clinical synovitis: development of a novel 6-joint protocol for feasible risk prediction

Ultrasound in anti-CCP+ at-risk individuals without clinical synovitis: development of a novel 6-joint protocol for feasible risk prediction

Rheumatoid arthritis: prediction of future clinically-apparent disease, and prevention

Multi‐Autoantibody Testing Identifies Expansion of Reactivity to Targeted Antigens Before a Diagnosis of Rheumatoid Arthritis

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